1. Field of the Invention
The present invention relates, in general, to noninvasive sensing of biological analytes in the capillary vessels and in interstitial fluid. More specifically, the present invention relates to a method and an apparatus for the determination of blood glucose, lipids and/or alcohol concentration at regular short intervals on a continuous basis or on demand.
2. Description of Related Art
Diabetes is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. The Diabetes Control and Complications Trial (DCCT), a ten year clinical study conducted between 1983 and 1993 by the National Institute of Diabetes and Digestive and Kidney Diseases, demonstrated a direct positive correlation between high average blood glucose levels, known as hyperglycemia and the development of devastating complications of the disease that affect the kidneys, eyes, nervous system, blood vessels and circulatory system. Treatment includes insulin injections, oral medication, diet control and exercise. Adjustment of the user's regimen by a physician to control hyperglycemia requires routine self-monitoring of glucose levels three or more times per day. Currently persons with diabetes measure their glucose levels by using invasive blood glucose instruments that measure glucose using expensive disposable test strips where a small sample of blood obtained from a finger or the forearm is applied. The procedure is very painful and often results in chronic nerve ending damage. This is one reason many diabetes patients forego monitoring risking the development of serious complications.
Many prior art systems utilize diffuse reflectance spectroscopy to determine blood glucose concentration in tissue. For instance, U.S. Pat. No. 6,097,975 to Petrovsky et al. discloses an apparatus and method for non-invasively measuring blood glucose concentration. The apparatus projects a beam of light (2050-2500 nm) to a selected area of the body that is rich in blood vessels, such as the inner wrist or ear lobes. The projected pulse of light is transmitted through the skin, tissues and blood vessels, partially absorbed by glucose in the blood and partially scattered, diffused and reflected off of irradiated structures back through the blood vessels, tissue and skin. The luminous energy of the reflected light is then collected by a receiving detector, converted to an electrical signal proportional to the glucose concentration in the blood of the subject and analyzed. The wavelength range of the preferred embodiment disclosed in this reference utilizes the wavelength range of 2050-2500 nm.
U.S. Pat. No. 6,016,435 to Maruo et al. discloses a device for non-invasive determination of a glucose concentration in the blood of a subject. The device includes a light source, a diffraction grating unit as a spectroscope of the light provided by the light source and a stepping motor unit for controlling a rotation angle of the diffraction grating to provide near-infrared radiation having successive wavelengths from 1300-2500 nm. The device further includes an optical fiber bundle having a plurality of optical fibers for projecting the near-infrared radiation onto the skin of a subject and a plurality of second optical fibers for receiving the resulting radiation emitted from the skin. A light receiving unit is connected to the second optical fibers and a spectrum analyzing unit determines the glucose concentration in the blood through the use of spectrum analysis based on information from the light receiving unit. This invention differs from the present invention in that it utilizes a continuous spectrum lamp and a diffraction grating with mechanically moving parts.
U.S. Pat. No. 5,533,509 to Koashi et al. discloses an apparatus for non-invasive measurement of blood sugar level. The apparatus includes a wavelength-variable semiconductor laser that tunes in small ranges around wavelengths of interest producing a beam that is separated into two optical paths with a beam splitter and an integrating sphere that collects laser light transmitted or reflected after passing along an optical path and made incident on an examined portion of skin in which the blood glucose level is determined by examining the derivative of the absorbance spectrum. The present invention differs from this reference in that the skin is probed over the entire range with a plurality of wavelengths and not just certain wavelengths, and the absorbance spectrum, not the derivative of the absorption spectrum, is used to determine glucose concentration.
United States Patent Application Publication No. 2005/0250997 to Takeda et al. discloses an apparatus for determining a concentration of a light absorbing substance in blood. The apparatus includes a plurality of photo emitters that emit light beams having different wavelengths toward a living tissue. A photo receiver is adapted to receive the light beams which have been transmitted through or reflected from the living tissue. However, the preferred embodiment of this invention calls for only two light emitting diodes; one at 680 nm and one at 940 nm.
United States Patent Application Publication No. 2005/0256384 to Walker et al. discloses a non-invasive glucose sensor including at least one laser (Vertical Cavity Surface Emitting Laser (VCSEL) or edge emitting) and at least one photo detector configured to detect emissions from the emitter. The glucose sensor further includes a controller driving one or more emitters by shifting emitter wavelength by 1-2 nm from a group of selected wavelengths having center wavelengths of 1060 nm, 980 nm, 850 nm, 825 nm, 800 nm, 780 nm and 765 nm. This enables measurement of absorption at a plurality of wavelengths and derivation of a glucose concentration measurement from the absorption measurement values. The wavelength range of operation of this apparatus is outside the wavelength range of the present invention.
U.S. Pat. No. 5,703,364 to Rosenthal discloses a method for performing near-infrared (NIR) quantitative analysis. The method includes the steps of providing NIR radiation at a plurality of different wavelengths (600-1100 nm) for illumination of an object to be analyzed and varying the amount of time that radiation at each wavelength illuminates the subject according to the output level of radiation at each wavelength so as to provide substantially similar detection data resolution for each of the plurality of wavelengths. The wavelength range of operation of this apparatus is outside the wavelength range of the present invention.
U.S. Pat. No. 6,816,241 to Grubisic discloses a solid-state spectrophotometer for non-invasive blood analyte detection that employs a plurality of Light Emitting Diodes (LED(s)) that emit at distinct, but overlapping, wavelengths in order to generate a continuous broad radiation spectrum and a linear detector array. It therefore differs from the present invention in that it uses an array of LEDs and an array of detectors.
Accordingly, a need exists for a system for the non-invasive sensing of glucose in a human subject that utilizes a pulsable and selectable wavelength, a selectable intensity monochromatic laser radiation source, involves a spectroscopic referencing scheme that does not require mechanical moving parts, and provides an improved instrument baseline stability by utilizing a dual-beam-double-reference spectrophotometer.